The present invention relates to a microchip and a particulate analyzing device. More particularly, the present invention relates to a microchip or the like for optically, electrically or magnetically analyzing the characteristics of particulates such as cells or microbeads in channels.
In recent years, microchips have been developed in which an area and/or a channel or channels for performing chemical and biological analyses are provided by application of micro-machining techniques used in the semiconductor industry. These microchips have begun to be utilized for electrochemical detectors in liquid chromatography, small electrochemical sensors in medical service sites, and the like.
Analytical systems using such microchips are called micro-TAS (micro-Total-Analysis System), lab-on-a-chip, bio chip or the like, and is paid attention to as a technology by which chemical and biological analyses can be enhanced in speed, efficiency and level of integration or by which analyzing devices can be reduced in size.
The micro-TAS, which enables analysis with a small amount of sample and enables disposable use of microchips, is expected to be applied particularly to biological analyses where precious trace amounts of samples or a multiplicity of specimens are treated.
An application example of the micro-TAS is a particulate analyzing technology in which characteristics of particulates such as cells and microbeads are analyzed optically, electrically or magnetically in channels arranged on microchips. In the particulate analyzing technology, fractional collection of a population satisfying a predetermined condition or conditions from among particulates on the basis of analytical results of the particulates is also conducted.
Patent Literature 1, for example, discloses “a particulate fractionation microchip having a channel for introducing particulate-containing solution, and a sheath flow forming channel arranged on at least one lateral side of the introducing channel.” The particulate fractionation microchip further has “a particulate measuring section for measuring the particulates introduced, at least two particulate fractionating channels disposed on the downstream side of the particulate measuring section so as to perform fractional collection of the particulates, and at least two electrodes disposed in the vicinity of channel ports opening from the particulate measuring section into the particulate fractionating channels so as to control the moving direction of the particulates.”
The particulate fractionation microchip disclosed in Patent Literature 1, typically, is so designed that fluid laminar flows are formed by a “trifurcated channel” having a channel for introducing a particulate-containing solution and two sheath flow forming channels (see “FIG. 1” of the literature).
FIGS. 17A and 17B show a trifurcated channel structure according to related art (FIG. 17A), and sample liquid laminar flows formed by the channel structure (FIG. 17B). In the trifurcated channel, a sample liquid laminar flow passing through a channel 101 in the direction of solid-line arrow in FIG. 17A can be sandwiched, from the left and right sides, by sheath liquid laminar flows introduced through channels 102, 102 in the directions of dotted-line arrows in the figure. By this, as shown in FIG. 17B, the sample liquid laminar flow can be fed through the center of the channel. Incidentally, in FIG. 17B, the sample liquid laminar flow is depicted in solid lines, and the channel structure in dotted lines.
According to the trifurcated channel shown in FIGS. 17A and 17B, the sample liquid laminar flow is sandwiched by the sheath liquid laminar flows from the left and right sides, whereby with respect to the sandwiching direction (the Y-axis direction in FIGS. 17A and 17B), the sample liquid laminar flow can be fed in the state of being deflected to an arbitrary position in the channel. With respect to the vertical direction (the Z-axis direction in FIGS. 17A and 17B) of the channel, however, it has been very difficult to control the sample liquid feeding position. In other words, in the trifurcated channel according to related art, it has only been possible to form the sample laminar flow that is oblong in the Z-axis direction.
Therefore, the microchip having the trifurcated channel according to related art has the problem that in the case where, for example, a particulate-containing solution as a sample liquid is made to flow through a channel and subjected to optical analysis, there would be a dispersion of the feeding position of the particulates in the vertical direction (depth direction) of the channel. Therefore, there has been the problem that the flowing speed of particulates differs depending on the feeding position of the particulates, variation of detection signals increases, and the accuracy of analysis is degraded.
Patent Literature 2 discloses a channel structure that introduces a sample liquid into the center of a sheath liquid laminar flow from an opening at the center of the channel through which the sheath liquid laminar flow is fed to thereby feed the sample liquid laminar flow being surrounded by the sheath liquid laminar flow (see FIGS. 2 and 3 of the literature). The channel structure enables the sample liquid to be introduced into the center of the sheath liquid laminar flow, thereby eliminating the dispersion of the feeding position of the particulates in the depth direction of the channel, so that the high accuracy of analysis can be obtained.
FIGS. 18A and 18B show a channel structure according to related art applied for introducing a sample liquid to the center of a sheath liquid laminar flow (FIG. 18A), and a sample liquid laminar flow formed by the channel structure (FIG. 18B). In this channel structure, the sheath liquid laminar flow is introduced into each of channels 102 and 102 in the direction of arrow T in FIG. 18A and fed to a channel 103. Then, the sample liquid fed to a channel 101 in the direction of arrow S can be introduced from an opening 104 to the center of the sheath liquid laminar flow fed through the channel 103. The sample liquid laminar flow can be thereby fed, being converged to the center of the channel 103, as shown in FIG. 18B. In FIG. 18B, the sample liquid laminar flow is depicted in solid lines, and the channel structure in dotted lines.
On the other hand, in Patent Literature 2, it is pointed out that, when introducing the sample liquid laminar flow into the sheath liquid laminar flow in such a channel structure, turbulence occurs in the sample liquid laminar flow, which raises the case where the sample liquid laminar flow is not a flat and stable laminar flow (see the rows 12 to 46 in the right column on page 4 of the literature). Note that “flat laminar flow” indicates a laminar flow converted in the depth direction (the Z-axis direction) of the channel in FIGS. 18A and 18B, and “non-flat laminar flow” indicates a laminar flow dispersed and spread in the depth direction of the channel.
In the above Patent Literature, it is proposed to provide the opening of the channel through which the sample liquid laminar flow is introduced with a pair of plate projections (see the reference numeral 18 in FIG. 10 of the literature) or the like in order to suppress the turbulence (wake) of the laminar flow at the merging portion of the sample liquid laminar flow and the sheath liquid laminar flows. The plate projections 18 extend from the opening wall of the channel through which the sample liquid laminar flow is introduced in the flowing direction of the sample liquid laminar flow and guides the sample liquid flowing out from the opening.